ATP-SENSITIVE POTASSIUM CHANNELS ARE INVOLVED IN ADENOSINE A(2) RECEPTOR-MEDIATED CORONARY VASODILATATION IN THE DOG

Objective: The aim was to determine a role of ATP sensitive potassium (K-ATP) channels in adenosine A(2) receptor mediated coronary vasodila tation in anaesthetised dogs in vivo. Methods: Coronary blood flow in the left circumflex coronary artery, aortic pressure, and left ventric ular pressure were measured during intracoronary infusions of the drug s into the left circumflex artery. Results: A non-selective A(2) recep tor agonist NECA (5'-N-ethylcarboxamidoadenosine) at 10(-10)-10(-8) mo l.min(-1) before and after an A(1) receptor antagonist DPCPX (8-cyclop entyl-1,3-dipropylxanthine) increased coronary blood flow in a dose de pendent manner, without affecting other haemodynamic variables. Gliben clamide at 10 mu g.kg(-1).min(-1), which did net alter baseline haemod ynamic variables, markedly inhibited the increases in coronary blood h ow caused by NECA alone and after DPCPX (p<0.01). A non-selective aden osine receptor antagonist 8-phenyltheophylline abolished the NECA indu ced increases in coronary blood flow after DPCPX. These results sugges t that A(2) receptor mediated coronary vasodilatation was mediated lar gely by opening of K-ATP channels. Glibenclamide did not alter the inc rease in coronary blood flow evoked by forskolin or acetylcholine, sug gesting that K-ATP channels may not be involved in coronary vasodilata tion induced by activation of adenylate cyclase or guanylate cyclase. Furthermore, DPCPX increased basal coronary blood flow, which was bloc ked by 8-phenyltheophylline and by glibenclamide, suggesting that it m ay have unmasked A(2) receptor mediated coronary vasodilatation by inh ibiting the A(1) receptor mediated vasoconstricting action of endogeno us adenosine. Conclusions: Opening of K-ATP channels may be involved i mportantly in adenosine A(2) receptor mediated coronary vasodilatation in canine hearts.